This proposal represents one-half of a jointly proposed, dual-site proposal with Dr. Arthur Barsky in Boston to conduct a randomized, placebo-controlled clinical trial comparing the efficacy of cognitive/behavioral therapy (CBT), fluoxetine (FLX), and their combination, in the treatment of DSM IV hypochondriasis. Our two centers have complementary areas of expertise; one center (Boston) has shown CBT to be efficacious and one (NY) has shown fluoxetine to be efficacious. However, the relative and combined efficacy of CBT and drug treatment for hypochondriasis has never been studied. Each site will enroll 132 subjects from among the primary care patients and community residents and will conduct identifical treatments and assessments. After baseline assessments, eligible patients will be randomized to 1 of 4 treatment conditions: CBT; FLX; CBT + FLX; or pill placebo. Patients receiving medication will also receive supportive therapy. After 12 weeks of treatment, patients rated as at least minimally improved will continue in treatment for an additional 12 weeks to the primary study endpoint at 24 weeks. A long-term, naturalistic follow-up will be completed on all patients at 48 weeks. Non-responders at 12 weeks will be removed from the study and treated openly. The primary statistical analyses will be conducted on an intent-to-treat basis. The primary hypotheses are: (1) Both CBT alone and FLX alone will be more effective than placebo in reducing hypochondriacal such that symptoms; (2) CBT and FLX will not differ in effectiveness; and (3) A pattern of efficacy will be demonstrated FLX+CBT is superior to each of the single active treatments and in turn both are superior to the placebo treatment at week 24. Secondary analyses will examine differential rapidity of response, baseline predictors of response, differential attrition and long-term durability. The results promise to yield definitive treatment recommendations for this major public health disorder. Most recently, the 2004 National Advisory Mental Health Council's Workgroup on Clinical Trials stated: "the portfolio must include more research in this area".